GnRH secretion into CSF in rams treated with a GnRH antagonist.
The equilibrium of the brain-pituitary-testicular axis is controlled by negative feedback exerted primarily through changes in the circulating concentrations of gonadal steroids. This is usually studied in gonadectomised animals treated with single large doses or constant low levels of exogenous steroid. However, the feedback system probably also contains dynamic components, perhaps expressed as delays to changes in GnRH secretion following a change in steroid concentration. These delays must be measured without interference from surgical procedures, including anaesthesia, bias associated with changes in pituitary responsiveness (which affect the efficiency of pulse detection), and chronic side-effects of gonadectomy. We used a GnRH antagonist ['Antarelix': Ac-D-Nal, D-Cpa, D-Pal, Ser, Tyr, D-Hci, Leu, Lys-(iPr), Pro, D-Ala-NH2] to transiently block LH and steroid secretion (in effect, inducing and reversing castration) in mature male sheep, and measured GnRH secretion into cerebrospinal fluid (CSF) in the third cerebral ventricle. The CSF was withdrawn with a peristaltic pump at a rate of 2 ml/h and pooled every 20 min. Jugular plasma was sampled every 20 min and analysed for testosterone and LH pulses. The antagonist (500 microg i.v.) was injected after 6 h of baseline sampling and the study continued for a further 24 h. The pulses of LH and testosterone disappeared shortly after antagonist injection, with delays of 20 +/- 12 min for LH and 80 +/- 29 min for testosterone. This led to an increase in GnRH pulse frequency, starting 300 +/- 54 min after antagonist injection. Secretion of LH and testosterone pulses resumed at 553 +/- 38 and 530 +/- 30 min (after antagonist injection), and GnRH pulse frequency returned to baseline values after 170 +/- 42 min (relative to LH) and 117 +/- 35 min (relative to testosterone). The consistent nature of these responses across the group of animals suggests that this can be used to test the effects of exteroceptive factors on the dynamics of negative feedback.
Blache
D
D
Faculty of Agriculture (Animal Science), University of Western Australia, Nedlands.
Chagas
L M
LM
Caraty
A
A
Deghenghi
R
R
Delaleu
B
B
Blackberry
M A
MA
Martin
G B
GB
D000818:Animals; D005246:Feedback / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D012756:Sheep; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone